CN1162250A - Ultrasonic process and circuits for carrying out this process - Google Patents

Ultrasonic process and circuits for carrying out this process Download PDF

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Publication number
CN1162250A
CN1162250A CN95195991A CN95195991A CN1162250A CN 1162250 A CN1162250 A CN 1162250A CN 95195991 A CN95195991 A CN 95195991A CN 95195991 A CN95195991 A CN 95195991A CN 1162250 A CN1162250 A CN 1162250A
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processing method
ultrasonic processing
ultrasonic
contrast agent
frequency
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CN1154436C (en
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沃尔克玛·乌伦多夫
克里斯蒂安·豪夫曼
托马斯·夫里兹舍
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Bayer AG
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Schering AG
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/48—Diagnostic techniques
    • A61B8/481—Diagnostic techniques involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
    • G01S7/00—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00
    • G01S7/52—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00
    • G01S7/52017—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00 particularly adapted to short-range imaging
    • G01S7/52023—Details of receivers
    • G01S7/52036—Details of receivers using analysis of echo signal for target characterisation
    • G01S7/52038—Details of receivers using analysis of echo signal for target characterisation involving non-linear properties of the propagation medium or of the reflective target

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Nonlinear Science (AREA)
  • Computer Networks & Wireless Communication (AREA)
  • General Physics & Mathematics (AREA)
  • Radar, Positioning & Navigation (AREA)
  • Remote Sensing (AREA)
  • Ultra Sonic Daignosis Equipment (AREA)
  • Investigating Or Analyzing Materials By The Use Of Ultrasonic Waves (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Measurement Of Velocity Or Position Using Acoustic Or Ultrasonic Waves (AREA)

Abstract

The invention concerns a process for the selective graphic reproduction and/or the evaluation of the Doppler spectrum of objects, e.g. biological organs and tissue, which offer limited resistance to sound intensities, the process consisting of an ultrasonic process in which a material is introduced into the area under investigation which is to be exposed to acoustic radiation. Radiated ultrasound waves generate non-linear oscillations in the area under investigation, and the signal is evaluated by an ultrasonic transducer. The invention also concerns a circuit for carrying out this process.

Description

Supersound process and the circuit of carrying out this processing
The present invention relates to the multispectral ultrasonic processing method of reining in frequency spectrum that imaging and analysis have the object of limited anti-sound degree, and the circuit of carrying out these processing.
In ultrasonic technique, ultrasound wave is radiated an inspection area so that carry out imaging selectively and/or analyze the multispectral frequency spectrum of reining in.In the processing and equipment of the testing of materials and inspection biological tissue, the sound head that generally uses emittor/receiver to combine.Crystal and electronic equipment by agitator are fixed an audio frequency (f 0), it is identical to transmitting and receiving.The about 3-7MHZ of sound head frequency range of a typical 5MHZ, mid frequency f 0=5MHZ.For the situation of pulse echo technology, in identical frequency range, receive reflection and/or backscattered signal.This equipment and processing also are applied in the inspection of the physiological tissue that uses acoustic contrast agent.For the component of signal outside given frequency range, for example become the vibration of harmonic relationships with the frequency of being launched, checking and other for example multispectral imagings of reining under the measurement situation and being not used in object.In addition, for covering a bigger frequency range, processing of the prior art and device systems use several sound heads of during checking changing.EP-A2-0147955 discloses a kind of supersound process, and wherein checked object is subjected to the effect of the low frequency pump fortune pulse of high frequency measurement pulse and high sound pressure.
In analysis, the dependence of the utilization velocity of sound and pressure.Change pressure in the checked object by the pulse of pump fortune.
Measurement pulse on being superimposed upon in the pump fortune arteries and veins, phase place is changed, and is used for this analysis at last.Therefore the key factor of this processing of the prior art is a phase relation.There is not the analysis harmonic wave, subharmonic or ultraharmonics frequency.
In addition, in the processing of prior art, be necessary to analyze the reference signal of no pump fortune pulse so that this phase shift of energy measurement.
According to the pressure of measuring in known a kind of processing of EP-A3-0072330 in the inspected object.For this reason, only produce bubble in the inspected object by acted on by ultrasound wave.To produce a low frequency ultrasound source in checked object, its typical frequency range is about 100MHZ-20MHZ, and under the low pressure situation, in gasless solution, steam will bubble, if dissolved gases is perhaps arranged, gas will bubble.
Increase ultrasonic power till cavitation erosion (Cavitation) is bubbled in checked object.This bubble can be very big (observing with the naked eye easily), be retained in the sound field, and causes the thromboembolism risk.If they are created in the tissue, with the reaction of following that occurs such as decompression sickness ran into.But, exist damaged risk for pulmonary especially owing to can not avoid spuious low-frequency ultrasonic waves.
EP-A2-0 068 399 has described a kind of method that is used for determining at tissue ultrasonic attenuation or absorption.Determine the timely variation of backscattered average frequency for this reason, or in the spatial variations of the direction of propagation.Because decay changes approximately in proportion with frequency, when the propagation distance of duration pulse of ultrasonic energy increased, average frequency was partial to lower frequency at leisure.This from f TTo f CAnd f RSkew be relatively small amount.
In the method for pressing US-A-3 640 271, measure blood pressure and blood flow rate.To inject diameter for this reason and be controlled at the interior special-purpose bubble of 10-100 mu m range, and determine their resonant frequency before injection and after injecting.This available damping transducer and frequency scanning, or use is from the realization excited by impact of faint damping transducer.According to the size of bubble, must use the frequency in the 60-600KHZ scope, promptly wavelength is from 2.5-25mm.Use big bubble, so they can not pass through blood capillary.The speed of bubble can be measured or according to measuring by the time between two points with Doppler effect.
People are from list of references L.Germain, and J.O.N.Cheeke, J.Acoust.SOC.Am.83 (1988) 942 learn, for improving the image quality in the ultrasonic microscope, use the higher hamonic wave of driving frequency.But, for this reason must radiation very the ultrasound wave of high-amplitude is so that produce Non-Linear Vibration in this inspection area because non-linear, the energy of fundamental vibration is converted into higher harmonic oscillation.
This list of references resembles list of references (W.K.Law etc., Journal of the AcousticalSociety of America, vol.69, No.4,1981.4, pp.1212) relate to ultransonic nonlinear propagation like that, only in water and tissue, producing under the high strength condition.
Under the situation of nonlinear propagation, do not produce the subharmonic vibration, and some centimetres minimum range generation is afterwards only propagated in harmonic vibration in medium.
Yet those methods can not be used in ultrasonic examination, for example, use the frequency of 1-10MHZ scope, object for example particularly biological tissue can not resist the high sound intensity.
The objective of the invention is to expand the application scenario of supersound process, make it be used for the anti-sound intensity limited object, particularly biological tissue, so that imaging and analyze the multispectral frequency spectrum of reining in selectively, provide the circuit of these methods of realization simultaneously,
Purpose of the present invention realizes by following method.
By introducing material or the medium that produces nonlinear effect, remove and obtain driving frequency f to the test zone that is exposed to the harmless low sound intensity 0Outside, obtain the strong scattering of big frequency deviation and/or transmit.These scatterings and/or the harmonic wave (2f that transmits and concentrate on driving frequency especially 0, 3f 0...), subharmonic (1/2f 0, 1/3f 0, 3/4f 0) and ultraharmonics (3/2f 0, 5/4f 0...) on.According to the method, energy radiation low frequency can obtain darker penetrance thus, and can analyze the received signal of higher frequency.
By advanced mode, might select to analyze be subjected to component of signal that the material quoted or medium produce and selectively expression with the area of those media fillings, and need not to seek before using these materials or medium and the difference between the back two or more conditions that write down, and original technology is necessary.Particularly, the Doppler effect that has produced can be analyzed and needn't artificially simulate.
Advantageously, the nonlinear scattering thing is introduced to the inspection area, and the agent material of the contrast agent of a kind of non-linear ultrasonic solution or aerosol form, particularly microbubble or generation microbubble also can be introduced the inspection area.
For example disclosed dose of material is suitable non-linear ultrasonic contrast agent in EP 0 365 457, and at this as a reference, it is based on the galactose microgranule that comprises fatty acid.
But under following some condition that will describe in detail, at this DE 38 03972 as a reference, the contrast agent described in WO 93/25242 and the WO 94/07539 also suits.These agent material packages are drawn together the micropartical of being made up of gas core and polymeric shell and are expressed relative isodynamic characteristic.Under press strip spare in a low voice, they express the linear inverse scattering properties, under than the high sound pressure condition (its intensity is still located in the diagnostic area), express non-linear backscatter characteristic.Therefore they can use in non-linear domain according to the present invention.
Recommend a kind of microbubble float, in this suspended substance medium, have 10 -3%-30% solid matter (by weight) produces good effect.Reach by weight 10 by method of the present invention with by circuit of the present invention unusually -3The lowest limit of %.
Under certain conditions, especially when using DE 3803972, during agent material described in WO 93/25242 or the WO94/07539, can further increase sensitivity.These agent material are along with the width of cloth friend of radiation signal increases the superproportional level lifting of directly expressing instantaneous reverse signal above certain threshold unusually.Frequency (the f that this superproportional level promotes not only at radiation signal 0) can observe, and especially at 1/2f 0, 3/2f 0, 2f 0, 5/2f 0, 3f 0, 7/2f 0And 4f 0Can observe.Because 2f 0Back-scattered signal almost reach f under the foment being in above threshold 0Intensity, so this signal is by preferred detection.Excitation above threshold by in this diagnostic area might detect each microgranule or gas bubbles.Filling with for the space that the necessary dosage of detection zone can reduce under the contrast situation, is 10ppb up to microgranule (gas bubbles) concentration.Consider the relative density of 1ppb, corresponding about 1000 microgranules of this concentration, preferred 100-1000/1cm 3The inspection area.Also can use 1000-100,000/cm 3Concentration.
The reduction of contrast concentration will cause being reduced by the acoustic damping that this contrast agent causes, the penetration depth of radiation ultrasonic signal will increase in tissue thus.So also might hang down human body with the sound spectrograph inspection.
(or gas bubbles break) produces because of the ultrasonic radiation energy surpasses above-mentioned threshold value because the damage of microgranule, so this effect especially strengthens, causes microgranule (bubble) concentration in tissue to descend continuously in checking process.In this case, the nearest microgranule (bubble) of high sound source is at first destroyed.Along with the propelling of review time, ultrasonic signal also penetrates direct layer below, so might be by institute's even formation contrast of (organ) layer in a organized way.Because these processing especially occurred under the minimum contrast concentration situation every interior in very short time, therefore preferred modern data acquisition memory technology writes down detected signal.
Damaging microgranule (bubble) institute energy requirement changes with selected contrast agent.Energy must be greater than the threshold value of about 0.03MPa under the situation of disclosed contrast agent in EP 0 365 467, and for the situation of disclosed contrast agent in WO93/25242 and WO 94/07539, threshold value is about 0.1MPa.Determine by the professional and technical personnel easily that for the required energy of other contrast agent usually in the 0.01-1MPa scope, and this threshold value increases with the stability of bubble.
Can reduce the concentration of contrast agent by method of the present invention, this will further allow to be short of the imaging that does not for example belong to the human body of RES of microgranule.Like this, perfused tissue can be described by the contrast agent that detects in very thin blood vessel, this blood vessel since little cross section only load a small amount of contrast agent (for example, at cardiac muscle, liver, kidney, muscle, skin, optical fundus, lymph vessels, lymph node, urethra, flexible pipe, little and big body cavity).
If the contrast agent of detection site structure or organisation specific, then the advantage by processing of the present invention will be especially clearly.The contrast agent of this special use for example is disclosed among the WO 94/J7539.Because for this special contrast agent, have only the fraction that drops into dosage to touch the destination organization (organ) of requirement usually, it is problematic therefore detecting with common ultrasonic method.Yet might detect these a spot of contrast agent, this is unchallenged, as long as use by processing method of the present invention and circuit, if particularly with this contrast agent of energy emission that surpasses its threshold value.
In conjunction with above-mentioned contrast agent, on the basis that increases greatly by the sensitivity of processing of the present invention, might carry out imaging, except the lung just, cartilage portion and skeleton to all sites of human body.
For in conjunction with a kind of at patent application EP 0 365 457, WO 93/25242, the contrast agent of statement uses the distinctive sensitivity by the inventive method among DE38 03 972 or the WO 94/07539, uses the driving frequency of 1-22MHZ, preferred 2-5MHZ.Necessary acoustic pressure amplitude range is 0.01-5MPa, preferred 0.03-0.2MPa.The HF train of pulse has 1-50 pulse in the case, preferred 2-8 pulse.
In pressing method of the present invention, sonic transducer is encouraged by a forcing function generator, and the HF train of pulse that produces by its has adjustable amplitude and adjustable average frequency (f T), frequency range from 0.3MHZ to 22MHZ, preferred 1-11MHZ, cycle 0.5-20, preferred 1-5.Found to analyze the average frequency f that is lower than sonic transducer (emitter) TThe frequency advantageous particularly.
In analysis, select an interval at least and determine that by the analog or digital mode relevant frequency spectrum is favourable by a computer control gate circuit.Thus, the periodicity of the length of time window and each train of pulse can be adjusted between optimum frequency resolution and optimum spatial resolution.
Use might analyze under the harmonic excitation frequency situation easily by method of the present invention and mixed components (mixing products) situation under Doppler effect, the upper side band under 2 frequency excitation situations for example.This will allow to show low relatively flowing and not be subjected to that blood vessel wall is active to be influenced.
In addition, improved penetration depth and/or spatial resolution under the component of signal situation of analyzing harmonic signal components or on top being with, this is very useful in imaging and multispectral reining in the measurement.
Comprise by the circuit that is used to carry out said method of the present invention: a forcing function generator, its output is connected to the sound pitch damping by a T/R (emitter/receiver) switch, electric coupling, the agitator of wide band element of transducer, this switch carries out Synchronization Control by forcing function generator, the downstream link signal processing system.
In another embodiment of circuit, forcing function generator is connected to the input of transducer, and its outfan is connected to signal processing system.
In above-mentioned first kind of situation, when the T/R switch transition when " emission ", the train of pulse that is produced by forcing function generator is added to the agitator of transducer, and when the T/R switch is put " reception ", is sent to analytical system by the signal of this transducer reception.For second kind of situation, the input and output of transducer separate, so do not need the T/R switch.
Use average frequency f TElement of transducer greater than the upper limit of working range is particularly advantageous.The structure of its element of transducer is such, and the sound intensity of its emission as the function of frequency, is being lower than excitation or average frequency f TFrequency range in have positive first order derivative to frequency, this derivative is near constant especially in working range, perhaps the sound intensity this in working range, have a fixed value.Owing in this working range,,, can compensate similar frequency response to a great extent when carrying out damping especially standing hyperacoustic inspection area near linear frequency response.Because sort circuit and employed conversion might change the frequency that is used to check and not change sound head.In addition, to the spectrum analysis of material behavior the time, the special optimum ratio that can select spatial resolution and frequency resolution when analyzing for tissue characteristics.
Can carry out easily by processing method of the present invention by a kind of circuit, sort circuit has the multicomponent transducer, and this multicomponent transducer is pressed Phase delay mode received signal, so that excute phase array or dynamic focusing are handled.In this circuit, the output of forcing function generator is by n road signal distributor, n computer-controlled time delay circuit and n T/R switch are connected to the wide-band transducer element that n sound is subjected to the electric coupling of damping strongly, and its each output is connected to m road signal by n T/R switch and divides device.Described switch is by forcing function generator or by computer control.These m road signal distributors each by m time delay circuit be used for the fixed or variable circuit that frequency band is selected, and also be connected to the system that is used for m the selective further processing of frequency band by being used for phasing summing circuit and signal distribution circuit (if appropriate).
For further solving problem of the present invention, introduce a kind of material to standing hyperacoustic inspection area, by of the region generating Non-Linear Ocsillation of this material at radiate supersonic wave, have one or more controlled element of transducers alone or in combination, the broadband, sound is obstructed strongly, the ultrasonic transducer of electric coupling is encouraged by two HF trains of pulse, inequality and the upper limiting frequency that is lower than working range of its driving frequency half, the combination of the signal of these two driving frequencies, particularly they and difference frequency according to ultrasonic transducer receive from the inspection area reflection or analyze from the backscattered signal in this zone.In order to reach above-mentioned threshold value, preferably one of described frequency surpasses top threshold value.
In above method, the radiation of two signals that separate produces a stronger received signal, and its frequency is the combination of the frequency of radiation signal, particularly itself and or difference frequency.Since can obtain higher spatial resolution and especially to sensation of frequency interest.In the method, transducer can be with two HF trains of pulse excitations, but also can be with two element of transducers that separate of HF train of pulse de-energisation, and the average frequency of these HF trains of pulse is inequality and less than the upper limiting frequency of working range half.
Owing to press non-linear that the present invention produces, for example use f 0≈ f pTwo low frequency signals of ≈ 2MHZ are at f 0+ f pPromptly work as with identical power I near the signal ratio that is received on the frequency of 4MHZ 0, I p, only use to have frequency f 0+ f pThe resulting received signal that transmits strong.This phenomenon allows to have darker penetrance on high observing frequency.
Operable generation nonlinear material or medium can be identical with used material and the medium of the harmonic frequency of analyzing driving frequency.Might use substantially the same component, but need additional the 2nd HF generator.
Have under the multicomponent transducer situation at circuit, for reduction is radiated the mean power of inspection area, this secondary signal is always along the emission of first sense, and 1-2 cycle approximately in advance, and lasts till that first burst signal finishes.For this reason, be subjected to the influence of reasonable time delay circuit, make,, and first transmitting and be launched on the identical direction with this by the identical element of transducer in the sound head by after the T/R switch from the secondary signal of second generator.Afterwards this circuit matrix be received in frequency on signal.The T/R switch by the duration longer second transmit control.
Inventive embodiment describes with reference to the figure in the accompanying drawing in following description, wherein:
Fig. 1 represents square circuit diagram,
Fig. 2 represents the sectional view of a sampling container,
Fig. 3 represents the sound power of transducer and the relation of frequency,
The figure of Fig. 4-9 expression back-scattered signal,
Figure 10 represents the another one square circuit diagram,
Figure 11-13 expression when use in WO93/25242 during disclosed a kind of contrast agent, the figure of back-scattered signal (temporal resolution) and their frequency spectrum (frequency resolution) under different sound intensity states.
Figure 14 represents when using in WO93/25242 disclosed a kind of contrast agent, at 2f 0Scattered signal and the relational graph of the sound intensity.
For producing the signal that can further handle shown in Fig. 4-9, the sampling container shown in the circuit shown in Fig. 1 and Fig. 2 is used together, and the broadband sound head has the power characteristic shown in Fig. 3.
Be created in working range f by forcing function generator 1 0Min-f 0Max (f 0Min=0.3MHZ＜f 0＜f 0Max=22MHZ) multiple transmitted pulse of the changeable frequency and the cycle of adaptive-bandwidth-HF train of pulse, bandwidth varying is provided by several n of the sinusoidal period of every train of pulse: 0.5＜n＜20, transmitted pulse has degree of amplitude modulation, and this forcing function generator is by central computer 15 controls.This central computer 15 not only control survey process but also control its analysis.The output of generator 1 is directed into emitter/receiver switch 3, and as shown in the figure, this switch 3 is synchronous by generator 1.This T/R switch 3 also can directly be controlled by computer 15.The output of T/R switch 3 is connected to the broadband, coupling and the element of transducer 4 that focuses on.The concrete property of element of transducer is illustrated among Fig. 3.This transducer is a transducer that bandwidth is very wide, and does not produce interference resonance in working range; In addition, it has good electroacoustic impedance matching property and emission average frequency f T＞f 0Max.In the example of describing, f T=17MHZ.Transducer can also have the element of transducer that transmits and receives that separates on space and electrical property.Need not use T/R switch 3 in the case.Useful is, can also provide other element of transducer here, is used to launch second independent high-frequency signal.
The signal that is received by this element of transducer 4 is fed to broadband preamplifier 16 by the T/R switch, and for the situation that numerical frequency is analyzed, this amplifier is connected to anti-alias filter 17.Bandwidth＞the f of this broadband preamplifier 16 0Max.This wave filter 17 for example has the cut-off frequency of 10MHZ.The downstream of wave filter 17 is connected to a high-speed a/d converter, and wherein signal for example is digitized with Nyquist (Nyquist) frequency of 12.5MHZ.In a digital storage oscilloscope and central computer, carry out the further processing of signal.Recorder 19 is received in the A/D converter downstream.
Fig. 1 represents that A/D converter is triggered by forcing function generator 1.
Digitized signal self is stored and further handles by known way.This is useful for the correction of necessity especially.Also may shunting signal before the A/D conversion and only after further simulation process to signal digitalized.
Fig. 2 schematically illustrates the geometry of container 20, obtains measurement result given below with it.
As shown in Figure 2, sound head 4 is installed in this sampling container 20, and it is the broadband of a 17MHZ, coupling and the sound head that focuses on.Sampling container 20 is moisture.Sampling scope of two diaphragms, 21 restrictions, wherein the acoustic contrast agent of 10mg is dissolved in the water (H of 3ml 2O) in.
Measuring range internal reflection between diaphragm 21 and/or backscattered signal comprise some by transmitted pulse (frequency f 0) and introduce the composition that the nonlinear contrast agent of Measuring Object interacts and obtains.
Fig. 3 schematically illustrates the frequency band of the element of transducer in sound head.To see that in working range, the frequency response of agitator is almost linear.This frequency response in working range is used for compensating the similar frequency response of taking a sample in the checking process, yet the frequency response of taking a sample in the checking process also can then be proofreaied and correct by weighting.
In order to measure, the interested interval in time range is selected by computer-controlled gate circuit (not shown).Also may select the some time at interval.Relevant frequency spectrum is calculated by fft circuit (fast Fourier transform), and such frequency spectrum example is illustrated among Fig. 4-9.By selecting the reasonable time length of window, might between optimum frequency resolution and optimum spatial resolution, select.Fig. 4-8 is illustrated in the frequency spectrum on the time window.In order in these figure, clearly to represent spectrum component, selected a long-time window, spatial resolution is poor that is to say.The transmitted pulse of Fig. 4 explanation coupling window place reflection when contrast-agent-free over time.The f at sound head place 0=4.0MHZ+15dBm.Can see signal clearly at the 4MHZ place.The signal of representing on Fig. 4 top is an average power spectra, and it is to obtain after the low pass filter with 50MHZ nyquist frequency.
Fig. 5 represents the back-scattered signal from the sampling cavity of no acoustic contrast agent.Fig. 6 is illustrated in the additional back-scattered signal of 10mg contrast agent after seven minutes in the 3ml water.At 2 * f 0The place can see peak value clearly.
Fig. 7 is illustrated in the measurement result after 21 minutes under the condition that provides among Fig. 5.Frequency of utilization f 0=3MHZ.The frequency spectrum designation of clear record is 6.0 and first and second harmonic waves of 9.0MHZ.Fig. 8 represents with the additional back-scattered signal of ultrasonic media after 15 minutes of small concentration.At the frequency of utilization f of sound head place 0=4MHZ+20dBm.The frequency spectrum designation that Fig. 8 represents on top is at subharmonic 1/2f 0, ultraharmonics 3/2f 0And first harmonic 2f 0Has high relatively frequency resolution.
Fig. 9 represents the back-scattered signal from the linear ultrasonic contrast agent, the f of sound head 0=4.0MHZ+15dBm.Frequency spectrum only is illustrated in the backscatter on the driving frequency.
Can see that when generation interacted with nonlinear contrast agent, described frequency spectrum had amplitude clearly in frequency range, but does not occur in emission spectra.Might be according to the change of Doppler effect analysis spectrum.In order to use the circuit of in the embodiment that is described as supersound process, using, provide additional element for the situation of using phase place array formula sound head or dynamic focusing sound head.A kind of circuit table like this is shown among Figure 10.
Transmission signal from forcing function generator 1 (frequency f 0) is fed to n road signal distributor 5 by outfan 2.This signal is assigned to each element of transducer branch.In the embodiment shown, provide n transducer 4.Element of transducer 4.1 ..., 4.n passes through time delay circuit 7.1 ..., 7.n and by generator or computer-controlled T/R switch 3.1 ..., the 3.n received signal.Computer is provided with the time delay of each element of transducer by a kind of like this mode, makes on selected transmission frequency, produces desired directional characteristic on sound head.Same directional characteristic is provided with by corresponding time delay by receiver side's computer.By sound head 4.1 ..., the signal that 4.n receives passes through T/R switch 3.1 ..., 3.n is fed to preamplifier 6.1 ..., 6.n.Each preamplifier 6.1 ..., 6.n is added to m road signal distributor 10 with a signal, and its downstream is connected to suitable control or adjusts time delay circuit 11, and this delay circuit 11 is used for frequency band to circuit 12 feed signals and selects.What the downstream connected is the circuit that is used for the summation of frequency band phasing, if suitable, also is used for signal allocation.Carry out optionally further handling of each frequency band succeeded by known method.
Especially carry out and be different from f 0The analysis of frequency, 1/2f for example 0, 2f 0Calculating.
Time delay circuit can be changeable or fixed.Received signal produces the frequency band number that requires to the distribution of m road signal distributor, and its position and width are by the band filter adjustment.On the other hand, also can use a kind of so effective method of salary distribution, the i.e. same auxiliary signal mixing of received signal, this auxiliary signal is derived by initialize signal, and because of frequency band inequality, in such a way, back to back at different levels in, each frequency band can use similar elements work.
Around f 0Frequency band provide normally result, and other frequency band comprise frequency deviation big with the nonlinear properties component, this is owing to transmit with non-linear ultrasonic contrast agent results of interaction.
Can be according to known method, in the channel of any requirement or some parallel channels, carry out further treatment step and signal analysis.
For using two tranmitting frequency f 0And f P, second generator on Figure 10 right side is provided, this generator is connected to T/R switch 3.1 by signal distributor and line of time delay 15 ..., 3.n.This second generator 1 makes the spatial dimension irradiation ultrasound wave by at that time directional characteristic and the decision of receptor gating characteristic of tested object at least.Its structure can be such, and except that this broadband inverting element of describing, sound head comprises the similar broadband emission transducer that at least one is other, and this transducer preferably separates with other transducer electricity and independently launches generator 1 by second and present.Yet these two transmit also can be overlapping on electrical property by the mode that can use the same transducer element.
Disclosed a kind of contrast agent among Figure 11 (first half of figure) expression WO 93/55242, the time domain back-scattered signal when the 5MHZ train of pulse that with amplitude is 0.1MPa carries out faint excitation.
In the latter half of figure, reproduce the power spectrum of same signal.Can clearly see driving frequency f 0Signal (5MHZ); Harmonic wave, subharmonic and ultraharmonics signal draw by static state.
Figure 12 represents other experimental conditions but back-scattered signal during with 0.34MPa amplitude excitation identical with Figure 11.In this case, can clearly see the bigger time domain backscatter part of contrast agent.With regard to frequency discrimination, at 2f 0And 3f 0Detection signal clearly.
Back-scattered signal when Figure 13 represents with the 1MPa amplitude excitation.In time domain (first half of figure), the backscatter of contrast agent part is clearly greater than exomonental reflection, here, and 1 corresponding 50mV of scale mark.For power spectrum (Lower Half of figure), can know and see 1/2f 0, f 0, 3/2f 0, 2f 0, 5/2f 0, 3f 0, 7/2f 0Signal.Beat allly be, at 2f 0The signal at place has similar radiation frequency (f 0) intensity.
Figure 14 represents that back-scattered signal is when the driving frequency (f0) of different 2,3 and 4MHZ and the relation of sound radiation pressure.Equally, this situation is still used disclosed contrast agent in WO 93/25242.Beat all is that the intensity of backscatter detection signal increases the threshold value that surpasses about 40dB to become superproportional relation with excitation density.This specific character can be observed with similar method for other contrast agent, for example based on the micropartical of the galactose microgranule that comprises fatty acid, or the micropartical of air inclusion core and biodegradable polymer shell, as select its go up can in conjunction with have the molecule of dot structure and tissue characteristics.
All whole disclosed applications, patent, and the publication that quote front and back is at this as a reference.
According to above explanation, those skilled in the art can conclude fundamental characteristics of the present invention easily, and can make various changes and improvements of the present invention, so that it is suitable for various use occasions and condition, but do not break away from the spirit and scope of the present invention.

Claims (50)

1. the imaging of an object that is used for having in an inspection area limited anti-sound degree and analyze the multispectral ultrasonic processing method of reining in frequency spectrum selectively comprises step:
Object and a kind of acoustic contrast agent of need imaging are incorporated into described inspection area, this acoustic contrast agent comprises as the microvesicle of scattering object or because of the irradiation ultrasound wave and produces microvesicle, make this contrast agent that the Non-Linear Vibration of microvesicle is provided by this inspection area of radiating ultrasound wave radiation the time
Applying frequency is f 0Excitation HF train of pulse, with to having one or several separately or by the broadband of the element of transducer of group control, strong acoustic damping, the transducer of electrical property coupling carries out electric excitation, makes the inspection area be subjected to f thus 0For the amplitude of 1MHZ-22MHZ is enough to make the disruptive ultrasound wave of microvesicle at least a portion in the contrast agent or its generation,
By ultrasonic transducer receive from the inspection area reflection and from the backscattered ultrasonic signal in this zone, and handle the ultrasonic signal that receives so that further analyze, and
According to the reflection with backscattered ultrasonic signal, analyze driving frequency f at least 0Harmonic wave, one of subharmonic and ultraharmonics, and can select driving frequency f 0
2. the imaging of an object that is used for having in an inspection area limited anti-sound degree and analyze the multispectral ultrasonic processing method of reining in frequency spectrum selectively comprises step:
Object and a kind of acoustic contrast agent of need imaging are incorporated into described inspection area, this acoustic contrast agent comprises as the microvesicle of scattering object or because of the irradiation ultrasound wave and produces microvesicle, make this contrast agent that the Non-Linear Vibration of microvesicle is provided by this inspection area of radiating ultrasound wave radiation the time
Applying driving frequency is f 0And f PThe HF train of pulse so that to having one or several separately or by the broadband of the element of transducer of group control, strong acoustic damping, the transducer of electrical property coupling carries out electric excitation, wherein this driving frequency f 0And f PBe inequality, and each all is lower than half of upper limiting frequency of the working range of this ultrasonic transducer, and the amplitude of at least one driving frequency part microvesicle in this contrast agent or that produce by this contrast agent that is enough to break wherein.
By ultrasonic transducer receive from the inspection area reflection and from the backscattered ultrasonic signal in this zone, and handle the ultrasonic signal that receives so that further analyze, and
Analyze these two driving frequencies and or poor according to what reflect with backscattered ultrasonic signal.
3. according to the ultrasonic processing method of claim 1, wherein this contrast agent is such agent material, comprises
Based on the micropartical of fatty acids galactose microgranule, or
The micropartical that contains gas core and biodegradable polymer shell selectively can be in conjunction with the molecule with place, structure and/or tissue characteristics.
4. the ultrasonic processing method of claim 1, wherein driving frequency f 0Be 2-5MHZ.
5. the ultrasonic processing method of claim 1, wherein the acoustic pressure amplitude is 0.01MPa-5Mpa.
6. the ultrasonic processing method of claim 1, wherein the acoustic pressure amplitude is 0.03-1Mpa.
7. the ultrasonic processing method of claim 3, wherein 1-50 pulse of each HF transmitted in bursts.
8. the ultrasonic processing method of claim 3, wherein 2-8 pulse of each HF transmitted in bursts.
9. the ultrasonic processing method of claim 3 is used for diagnosis and shows blood vessel.
10. the ultrasonic processing method of claim 3 is used for diagnosis and shows blood capillary.
11. the ultrasonic processing method of claim 3 is used for diagnosis and shows cardiac muscle.
12. the ultrasonic processing method of claim 3 is used for diagnosis and shows liver.
13. the ultrasonic processing method of claim 3 is used for diagnosis and shows kidney.
14. the ultrasonic processing method of claim 3 is used for diagnosis and shows skin.
15. the ultrasonic processing method of claim 3 is used for diagnosis and shows muscle.
16. the ultrasonic processing method of claim 3 is used for diagnosis and shows the optical fundus.
17. the ultrasonic processing method of claim 3 is used for diagnosis and shows lymph vessels and/or lymph node.
18. the ultrasonic processing method of claim 3 is used for diagnosis and shows urethra.
19. the ultrasonic processing method of claim 3 is used to diagnose the little and/or big body cavity of demonstration.
20. the ultrasonic processing method of claim 3 is used for diagnosis and shows the fallopian tube flexible pipe.
21. the ultrasonic processing method of claim 20 is used to diagnose fertility.
22. the ultrasonic processing method of claim 1 is wherein analyzed 2f 0Signal.
23. the ultrasonic processing method of claim 1, wherein the test zone is a human body, in human body from the about 1000/cm of concentration of the microvesicle of contrast agent 3Or it is slightly little.
24. according to the ultrasonic processing method of claim 2, wherein contrast agent is such agent material, comprises
Based on the micropartical of the galactose microgranule of fatty acids, or
The micropartical that contains gas core and biodegradable polymer shell is selectively in conjunction with the molecule with place, structure and/or tissue characteristics.
25. the ultrasonic processing method of claim 2, wherein driving frequency f 0Be 2-5MHZ.
26. the ultrasonic processing method of claim 2, wherein the acoustic pressure amplitude is 0.01Mpa-5Mpa.
27. the ultrasonic processing method of claim 2, wherein the acoustic pressure amplitude is 0.03-1Mpa.
28. the ultrasonic processing method of claim 24, wherein 1-50 pulse of each HF transmitted in bursts.
29. the ultrasonic processing method of claim 24, wherein 2-8 pulse of each HF transmitted in bursts.
30. the ultrasonic processing method of claim 24 is used for diagnosis and shows blood vessel.
31. the ultrasonic processing method of claim 24 is used for diagnosis and shows blood capillary.
32. the ultrasonic processing method of claim 24 is used for diagnosis and shows cardiac muscle.
33. the ultrasonic processing method of claim 24 is used for diagnosis and shows liver.
34. the ultrasonic processing method of claim 24 is used for diagnosis and shows kidney.
35. the ultrasonic processing method of claim 24 is used for diagnosis and shows skin.
36. the ultrasonic processing method of claim 24 is used for diagnosis and shows muscle.
37. the ultrasonic processing method of claim 24 is used for diagnosis and shows the optical fundus.
38. the ultrasonic processing method of claim 24 is used for diagnosis and shows lymph vessels and/or lymph node.
39. the ultrasonic processing method of claim 24 is used for diagnosis and shows urethra.
40. the ultrasonic processing method of claim 24 is used to diagnose the little and/or big body cavity of demonstration.
41. the ultrasonic processing method of claim 24 is used for diagnosis and shows the fallopian tube flexible pipe.
42. the ultrasonic processing method of claim 24 is used to diagnose fertility.
43. the processing method of claim 2 is wherein analyzed the 2f of driving frequency at least 0Signal.
44. the ultrasonic processing method of claim 2, wherein the test zone is a human body, in human body from the about 1000/cm of concentration of the microvesicle of contrast agent 3Or it is slightly little.
45. the imaging of an object that is used for having in an inspection area limited anti-sound degree and analyze the multispectral ultrasonic processing method of reining in frequency spectrum selectively comprises step:
Object and a kind of acoustic contrast agent of need imaging are incorporated into described inspection area, this acoustic contrast agent comprises as the microvesicle of scattering object or because of the irradiation ultrasound wave and produces microvesicle, make this contrast agent that the Non-Linear Vibration of microvesicle is provided by this inspection area of radiating ultrasound wave radiation the time
Applying frequency is f 0Excitation HF train of pulse so that to having one or several separately or by the broadband of the element of transducer of group control, transducer strong acoustic damping, the electrical property coupling carries out electric excitation, makes the inspection area be subjected to frequency f thus 0Be 1-22MHZ, amplitude is equal to or greater than hyperacoustic effect of irradiation of a threshold value, and make increases from the relative driving frequency hypergeometric of the instantaneous back-scattered signal of contrast agent routinely.
By ultrasonic transducer receive from the inspection area reflection and from the backscattered ultrasonic signal in this zone, and handle the ultrasonic signal that receives so that further analyze, and
According to the reflection with backscattered ultrasonic signal, analyze driving frequency f at least 0Harmonic wave, one of subharmonic and ultraharmonics, and can select driving frequency f 0
46. the imaging of an object that is used for having in an inspection area limited anti-sound degree and analyze the multispectral ultrasonic processing method of reining in frequency spectrum selectively comprises step:
Object and a kind of acoustic contrast agent of need imaging are incorporated into described inspection area, this acoustic contrast agent comprises as the microvesicle of scattering object or because of the irradiation ultrasound wave and produces microvesicle, make this contrast agent that the Non-Linear Vibration of microvesicle is provided by this inspection area of radiating ultrasound wave radiation the time
Applying driving frequency is f 0And f PThe HF train of pulse so that to having one or several separately or by the broadband of the element of transducer of group control, strong acoustic damping, the transducer of electrical property coupling carries out electric excitation, wherein this two driving frequency f 0And f PBe inequality, and each all is lower than half of upper limiting frequency of the working range of this ultrasonic transducer, and wherein at least one driving frequency is equal to or greater than a threshold value, and make increases from relative at least one the driving frequency hypergeometric of the instantaneous back-scattered signal of contrast agent routinely.
By ultrasonic transducer receive from the inspection area reflection and from the backscattered ultrasonic signal in this zone, and handle the ultrasonic signal that receives so that further analyze, and
According to reflection and backscattered ultrasonic signal, analyze these two driving frequencies and or poor.
47. the imaging of an object that is used for having in an inspection area limited anti-sound degree and analyze the multispectral ultrasonic processing method of reining in frequency spectrum selectively comprises step:
Introduce to desire the object of imaging and a kind of acoustic contrast agent to the inspection area, this acoustic contrast agent comprises microvesicle or produces microvesicle because of the irradiation ultrasound wave.
Apply f 0Be the amplitude of 1-22MHZ be enough to break at least ultrasound wave of the part microvesicle that produces by contrast agent, and
According to the reflection with backscattered ultrasonic signal, analyze this driving frequency f at least 0Harmonic wave, one of subharmonic and ultraharmonics.
48. the imaging of an object that is used for having in an inspection area limited anti-sound degree and analyze the multispectral ultrasonic processing method of reining in frequency spectrum selectively comprises step:
Object and a kind of acoustic contrast agent of need imaging are incorporated into described inspection area, and this acoustic contrast agent comprises microvesicle or because of the irradiation ultrasound wave produces microvesicle,
Apply two supersonic frequencies, f 0And f P, these two frequencies are inequality, and each all is lower than half of upper limiting frequency of the working range of the ultrasonic transducer that produces ultrasonic energy, and frequency f at least wherein 0And f PIn one of have in the contrast agent that is enough to break or the amplitude of the part microvesicle that produces by this contrast agent,
According to the reflection with backscattered ultrasonic signal, analyze this two frequency f 0And f PAnd or poor.
49. the ultrasonic processing method of claim 1, wherein, the inspection area is a human body, and the concentration from the microvesicle of contrast agent is 1000-100 in this human body, 000 microvesicle/cm 3
50. the ultrasonic processing method of claim 2, wherein, the inspection area is a human body, and the concentration from the microvesicle of contrast agent is 1000-100 in this human body, 000 microvesicle/cm 3
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